Penn Researchers Create Drug To Help Target Attack On Cancerous Tumors

Cancer clinicians have long known that hypoxic tumors--which thrive in oxygen-starved environments--are much more resistant to radiation and chemotherapy than their non-hypoxic cousins. But until now, physicians have had difficulty assessing hypoxicity

"When we know which tumors are hypoxic, we'll be able to custom-tailor a patient's cancer treatment," says Gillies McKenna, MD, Chair of Radiation Oncology at the University of Pennsylvania Cancer Center. "This may mean prescribing a more aggressive form of therapy, such as modifying the way radiation is delivered, or giving radiation in combination with drugs designed to exploit the hypoxic nature of the tumor," says McKenna.

EF5, developed by Cameron J. Koch, PhD, Professor of Radiation Oncology, was recently approved by the FDA for a Phase I clinical trial at the University of Pennsylvania Medical Center.

Patients with early stage cervix tumors, located at the neck of the uterus, and soft tissue sarcomas, are given EF5 intravenously two days before their tumors are surgically removed or biopsied. During this time, EF5 attaches or "binds" to hypoxic tumor cells, but "washes out" of tumor regions that are oxygen-rich. A small portion of the tumor, removed at surgery, is then exposed to fluorescent monoclonal antibodies.* These antibodies fasten to the hypoxic regions in the tumor and highlight its oxygen content.

Sydney Evans, VMD, Assistant Professor of Veterinary Medicine, has spent the last several years demonstrating the safety and efficacy of EF5 in animal tumor models and says that EF5 has shown no toxicity in animal studies.

In the trial, a second method of measuring hypoxia is also employed where a thin needle electrode is inserted into the tumor to measure the oxygen content. The needle electrode measures the amount of oxygen along the track of the needle. "Using the needle electrode is currently considered the standard method for measuring the tumor's oxygen content. However, by using EF5 with the needle electrode, we will have more precise information as to the amount and location of the oxygen within the entire tumor. Hopefully, it will increase the accuracy of tumor hypoxia diagnosis," Koch explains.

In the future, Penn researchers hope to adapt the EF5 technique for use with the Positron Emission Tomography (PET) imaging, which will allow for a non-invasive procedure of identifying the oxygen content within the patient's tumor. "Applications of this drug are far-reaching," says Evans. "We'll be able to non-invasively examine the binding of EF5 for other diseases in which hypoxia occurs, such as heart attacks and strokes, in addition to the use in cancer."

###*The fluorescent monoclonal antibodies were developed by Dr. Edith M. Lord, of the University of Rochester Cancer Center.